Nuclear export of unspliced and singly spliced human immunodeficiency virus (HIV) RNA is one of the essential steps in the viral life cycle. It requires the specific and cooperative interaction and oligomerization of the viral encoded protein Rev with the structured RNA element Rev response element (RRE). This interaction is key to the viral ability to recognize its own genomic RNA among much more abundant host RNAs. Currently all anti-HIV drugs target viral proteins, rather than viral RNAs. The RRE presents a unique target for development of new compounds for treatment of HIV.